| First Author | Basu M | Year | 2024 |
| Journal | Nat Microbiol | Volume | 9 |
| Issue | 8 | Pages | 2160-2172 |
| PubMed ID | 38839984 | Mgi Jnum | J:360178 |
| Mgi Id | MGI:7787173 | Doi | 10.1038/s41564-024-01726-6 |
| Citation | Basu M, et al. (2024) mRNA-encoded Cas13 can be used to treat dengue infections in mice. Nat Microbiol 9(8):2160-2172 |
| abstractText | Dengue is a major global health threat, and there are no approved antiviral agents. Prior research using Cas13 only demonstrated dengue mitigation in vitro. Here we demonstrate that systemic delivery of mRNA-encoded Cas13a and guide RNAs formulated in lipid nanoparticles can be used to treat dengue virus (DENV) 2 and 3 in mice. First, we identified guides against DENV 2 and 3 that demonstrated in vitro efficacy. Next, we confirmed that Cas13 enzymatic activity is necessary for DENV 2 or DENV 3 mitigation in vitro. Last, we show that a single dose of lipid-nanoparticle-formulated mRNA-encoded Cas13a and guide RNA, administered 1 day post-infection, promotes survival of all infected animals and serum viral titre decreases on days 2 and 3 post-infection after lethal challenge in mice. Off-target analysis in mice using RNA sequencing showed no collateral cleavage. Overall, these data demonstrate the potential of mRNA-encoded Cas13 as a pan-DENV drug. |
